SNP Analysis of Endometriosis Candidate Genes

描述（由申请人提供）：子宫内膜异位症是一种了解不多的妇科疾病，定义为异位部位存在子宫内膜组织。这种情况的特点是严重的盆腔疼痛，性交困难，痛经和不孕症。子宫内膜异位症继续使数百万妇女丧失能力并影响其健康，生产力和生活方式，同时对医生和研究人员提出了挑战。子宫内膜异位症的病因仍然难以捉摸，尽管环境，免疫和遗传因素已被牵连。现有的有限治疗方法无法治愈，明确诊断需要手术，因为这种疾病没有特异性诊断测试。我们一直在研究波多黎各子宫内膜异位症的分子和遗传方面，目的是填补对这种疾病的认识的重要空白，特别是对西班牙裔人口的认识。我们实验室的初步研究表明，以前报道的子宫内膜异位症的遗传相关性在我们的人群中并不成立。这些发现强调了在不同人群中进行关联研究的重要性，因为遗传变异及其对疾病易感性的影响可能因种族背景而异。此外，我们还观察到，有或没有子宫内膜异位症家族的患者的遗传相关性不同。最后，我们使用DNA微阵列，消减杂交和遗传连锁分析，以确定候选基因/基因组区域，可能代表子宫内膜异位症的易感位点。我们假设候选基因的遗传变异与子宫内膜异位症的易感性有关。同时，我们假设家族性与散发性子宫内膜异位症患者的遗传相关性不同。因此，本建议的主要目标是阐明波多黎各人群中子宫内膜异位症遗传易感性的机制，并确定这些机制是否因家族史而异。识别这些变异对于更好地了解子宫内膜异位症的病因，设计特定的非侵入性诊断测试以及最终开发这种失能性疾病的治愈方法至关重要。由于子宫内膜异位症和不孕症，妊娠丢失和异位妊娠之间的重要联系，这些研究揭示的信息将极大地影响生殖科学领域，这是2010年健康人群报告（9-12）中解决的目标问题。

DESCRIPTION (provided by applicant): Endometriosis is a poorly understood gynecologic condition defined as the presence of endometrial tissue at ectopic sites. This condition is characterized by severe pelvic pain, dyspareunia, dysmenorrhea, and infertility. Endometriosis continues to incapacitate and affect the well being, productivity, and lifestyle of millions of women, whilst imposing a challenge to medical doctors and researchers alike. The cause of endometriosis remains elusive, although environmental, immunological and genetic factors have been implicated. The limited treatments available are not curative, and definitive diagnosis requires surgery, since there are no specific diagnostic tests for this disease. We have been studying the molecular and genetic aspects of endometriosis in Puerto Rico, with the purpose of filling an important gap in the knowledge of this disease in general, and also as its applies to the Hispanic population in particular. Preliminary studies in our laboratory have shown that previously reported genetic associations to endometriosis do not hold true in our population. These findings highlight the importance of carrying out association studies in different populations, since genetic variations and their involvement in disease susceptibility are likely to vary across ethnic backgrounds. Also, we have observed that genetic associations differ in patients with and without a family of endometriosis. Finally, we have used DNA microarrays, subtractive hybridization and genetic linkage analysis to identify candidate genes/genomic regions which potentially represent susceptibility loci for endometriosis. We hypothesize that genetic variations in candidate genes are associated with susceptibility to endometriosis. Also, we hypothesize that genetic associations differ in patients with familial versus sporadic endometriosis. The main goal of the present proposal, therefore, is to elucidate the mechanisms involved in the genetic susceptibility to endometriosis in a Puerto Rican population, and to determine if those mechanisms vary according to family history status. Identification of such variations is of critical importance to better understand the etiology of endometriosis, to design specific non-invasive diagnostic tests and, ultimately, to develop a cure for this incapacitating condition. Due to important links between endometriosis and infertility, pregnancy loss and ectopic pregnancy, the information uncovered by these studies will greatly impact the field of reproductive science, a target issue addressed in the Healthy People 2010 report (9-12).